Persistence of atopic dermatitis (AD): A systematic review and meta-analysis

Published:August 18, 2016DOI:


      Previous studies found conflicting results about whether childhood atopic dermatitis (AD) persists into adulthood.


      We sought to determine persistence rates and clinical factors associated with prolonged AD.


      A systematic review was performed in MEDLINE, EMBASE, Scopus, GREAT, LILACS, Web of Science, Academic Search Complete, and Cochrane Library. Meta-analysis was performed using Kaplan-Meier plots and random-effects proportional hazards regression.


      In total, 45 studies including 110,651 subjects spanning 434,992 patient-years from 15 countries were included. In pooled analysis, 80% of childhood AD did not persist by 8 years and less than 5% persisted by 20 years after diagnosis (mean ± SE: 6.1 ± 0.02 years). Children with AD that persisted already for more than 10 years (8.3 ± 0.08 years) had longer persistence than those with 3 (3.2 ± 0.02 years) or 5 (6.8 ± 0.06 years) years of persistence. Children who developed AD by age 2 years had less persistent disease (P < .0001). Persistence was greater in studies using patient-/caregiver-assessed versus physician-assessed outcomes, female versus male patients (P ≤ .0006), but not in those with sensitivity to allergens (P = .90). Three studies found prolonged persistence with more severe AD.


      Some studies did not capture recurrences later in life.


      Most childhood AD remitted by adulthood. However, children with already persistent disease, later onset, and/or more severe disease have increased persistence.

      Key words

      Abbreviations used:

      AD (atopic dermatitis), CI (confidence interval), HR (hazard ratio)
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        • Margolis J.S.
        • Abuabara K.
        • Bilker W.
        • Hoffstad O.
        • Margolis D.J.
        Persistence of mild to moderate atopic dermatitis.
        JAMA Dermatol. 2014; 150: 593-600
        • Nankervis H.
        • Pynn E.V.
        • Boyle R.J.
        • et al.
        House dust mite reduction and avoidance measures for treating eczema.
        Cochrane Database Syst Rev. 2015; 1: CD008426
        • Fukuzumi T.
        • Kobayashi E.
        • Aoki T.
        • Sasai Y.
        • Kanamori S.
        • Yamada I.
        The influence of ageing and seasons on infantile eczema - a population-based cohort study of babies aged 4 months and 10 months.
        Arerugi. 2005; 54 ([in Japanese]): 455-463
        • Sangsupawanich P.
        • Chongsuvivatwong V.
        • Mo-Suwan L.
        • Choprapawon C.
        Relationship between atopic dermatitis and wheeze in the first year of life: analysis of a prospective cohort of Thai children.
        J Investig Allergol Clin Immunol. 2007; 17: 292-296
        • Morales E.
        • Garcia-Esteban R.
        • Guxens M.
        • et al.
        Effects of prolonged breastfeeding and colostrum fatty acids on allergic manifestations and infections in infancy.
        Clin Exp Allergy. 2012; 42: 918-928
        • Kawamoto N.
        • Fukao T.
        • Kaneko H.
        • et al.
        Total IgE at 6 months predicts remittance or persistence of atopic dermatitis at 14 months.
        Allergy Asthma Proc. 2013; 34: 362-369
        • Perkin M.R.
        • Strachan D.P.
        • Williams H.C.
        • Kennedy C.T.
        • Golding J.
        • ALSPAC Study Team
        Natural history of atopic dermatitis and its relationship to serum total immunoglobulin E in a population-based birth cohort study.
        Pediatr Allergy Immunol. 2004; 15: 221-229
        • Eller E.
        • Kjaer H.F.
        • Host A.
        • Andersen K.E.
        • Bindslev-Jensen C.
        Development of atopic dermatitis in the DARC birth cohort.
        Pediatr Allergy Immunol. 2010; 21: 307-314
        • Matsumoto K.
        • Shimanouchi Y.
        • Kawakubo K.
        • et al.
        Infantile eczema at one month of age is associated with cord blood eosinophilia and subsequent development of atopic dermatitis and wheezing illness until two years of age.
        Int Arch Allergy Immunol. 2005; 137: 69-76
        • Ballardini N.
        • Kull I.
        • Lind T.
        • et al.
        Development and comorbidity of eczema, asthma and rhinitis to age 12: data from the BAMSE birth cohort.
        Allergy. 2012; 67: 537-544
        • Amberbir A.
        • Medhin G.
        • Alem A.
        • Britton J.
        • Davey G.
        • Venn A.
        The role of acetaminophen and geohelminth infection on the incidence of wheeze and eczema: a longitudinal birth-cohort study.
        Am J Respir Crit Care Med. 2011; 183: 165-170
        • Purvis D.J.
        • Thompson J.M.
        • Clark P.M.
        • et al.
        Risk factors for atopic dermatitis in New Zealand children at 3.5 years of age.
        Br J Dermatol. 2005; 152: 742-749
        • Bleiker T.O.
        • Shahidullah H.
        • Dutton E.
        • Graham-Brown R.A.
        The prevalence and incidence of atopic dermatitis in a birth cohort: the importance of a family history of atopy.
        Arch Dermatol. 2000; 136: 274
        • Tariq S.M.
        • Matthews S.M.
        • Hakim E.A.
        • Stevens M.
        • Arshad S.H.
        • Hide D.W.
        The prevalence of and risk factors for atopy in early childhood: a whole population birth cohort study.
        J Allergy Clin Immunol. 1998; 101: 587-593
        • Kull I.
        • Bergstrom A.
        • Lilja G.
        • Pershagen G.
        • Wickman M.
        Fish consumption during the first year of life and development of allergic diseases during childhood.
        Allergy. 2006; 61: 1009-1015
        • Ekback M.
        • Tedner M.
        • Devenney I.
        • et al.
        Severe eczema in infancy can predict asthma development. A prospective study to the age of 10 years.
        PLoS One. 2014; 9: e99609
        • Illi S.
        • von Mutius E.
        • Lau S.
        • et al.
        The natural course of atopic dermatitis from birth to age 7 years and the association with asthma.
        J Allergy Clin Immunol. 2004; 113: 925-931
        • Singh A.G.
        • R.
        • Evans M.
        • et al.
        Risk factors for the persistent expression of atopic dermatitis in a high-risk birth cohort.
        J Allergy Clin Immunol. 2006; 117: S178
        • Gustafsson D.
        • Sjoberg O.
        • Foucard T.
        Development of allergies and asthma in infants and young children with atopic dermatitis–a prospective follow-up to 7 years of age.
        Allergy. 2000; 55: 240-245
        • van Asperen P.P.
        • Kemp A.S.
        The natural history of IgE sensitization and atopic disease in early childhood.
        Acta Paediatr Scand. 1989; 78: 239-245
        • Kissling S.
        • Wuthrich B.
        Follow-up of atopic dermatitis after early childhood [in German].
        Hautarzt. 1993; 44: 569-573
        • Shen C.Y.
        • Lin M.C.
        • Lin H.K.
        • Lin C.H.
        • Fu L.S.
        • Fu Y.C.
        The natural course of eczema from birth to age 7 years and the association with asthma and allergic rhinitis: a population-based birth cohort study.
        Allergy Asthma Proc. 2013; 34: 78-83
        • Carlsten C.
        • Dimich-Ward H.
        • Ferguson A.
        • et al.
        Atopic dermatitis in a high-risk cohort: natural history, associated allergic outcomes, and risk factors.
        Ann Allergy Asthma Immunol. 2013; 110: 24-28
        • Harpsoe M.C.
        • Basit S.
        • Bager P.
        • et al.
        Maternal obesity, gestational weight gain, and risk of asthma and atopic disease in offspring: a study within the Danish National Birth Cohort.
        J Allergy Clin Immunol. 2013; 131: 1033-1040
        • Burr M.L.
        • Dunstan F.D.
        • Hand S.
        • Ingram J.R.
        • Jones K.P.
        The natural history of eczema from birth to adult life: a cohort study.
        Br J Dermatol. 2013; 168: 1339-1342
        • Bohme M.
        • Soderhall C.
        • Kull I.
        • Bergstrom A.
        • van Hage M.
        • Wahlgren C.F.
        Filaggrin mutations increase the risk for persistent dry skin and eczema independent of sensitization.
        J Allergy Clin Immunol. 2012; 129: 1153-1155
        • Semic-Jusufagic A.
        • Gevaert P.
        • Bachert C.
        • Murray C.
        • Simpson A.
        • Custovic A.
        Increased serum-soluble interleukin-5 receptor alpha level precedes the development of eczema in children.
        Pediatr Allergy Immunol. 2010; 21: 1052-1058
        • von Kobyletzki L.B.
        • Bornehag C.G.
        • Breeze E.
        • Larsson M.
        • Lindstrom C.B.
        • Svensson A.
        Factors associated with remission of eczema in children: a population-based follow-up study.
        Acta Derm Venereol. 2014; 94: 179-184
        • Sumikawa Y.M.
        • A.
        • Yamashita T.
        A survey of the prevalence of atopic dermatitis in school students in Hokkaido.
        J Dermatol. 2014; 41: 72
        • Schmitt J.
        • Apfelbacher C.
        • Chen C.M.
        • et al.
        Infant-onset eczema in relation to mental health problems at age 10 years: results from a prospective birth cohort study (German Infant Nutrition Intervention plus).
        J Allergy Clin Immunol. 2010; 125: 404-410
        • Hua T.C.
        • Hwang C.Y.
        • Chen Y.J.
        • et al.
        The natural course of early-onset atopic dermatitis in Taiwan: a population-based cohort study.
        Br J Dermatol. 2014; 170: 130-135
        • Kurukulaaratchy R.
        • Fenn M.
        • Matthews S.
        • Hasan Arshad S.
        The prevalence, characteristics of and early life risk factors for eczema in 10-year-old children.
        Pediatr Allergy Immunol. 2003; 14: 178-183
        • Kekki O.M.
        • Scheynius A.
        • Poikonen S.
        • Koskinen A.
        • Kautiainen H.
        • Turjanmaa K.
        Sensitization to Malassezia in children with atopic dermatitis combined with food allergy.
        Pediatr Allergy Immunol. 2013; 24: 244-249
        • Filipiak-Pittroff B.
        • Schnopp C.
        • Berdel D.
        • et al.
        Predictive value of food sensitization and filaggrin mutations in children with eczema.
        J Allergy Clin Immunol. 2011; 128: 1235-1241.e5
        • Williams H.C.
        • Strachan D.P.
        The natural history of childhood eczema: observations from the British 1958 birth cohort study.
        Br J Dermatol. 1998; 139: 834-839
        • Novembre E.
        • Cianferoni A.
        • Lombardi E.
        • Bernardini R.
        • Pucci N.
        • Vierucci A.
        Natural history of “intrinsic” atopic dermatitis.
        Allergy. 2001; 56: 452-453
        • Wuthrich B.
        • Schmid-Grendelmeier P.
        Natural course of AEDS.
        Allergy. 2002; 57: 267-268
        • Wakamori T.
        • Katoh N.
        • Hirano S.
        • Kishimoto S.
        • Ozasa K.
        Atopic dermatitis, dry skin and serum IgE in children in a community in japan.
        Int Arch Allergy Immunol. 2009; 149: 103-110
        • Vowles M.
        • Warin R.P.
        • Apley J.
        Infantile eczema: observations on natural history and prognosis.
        Br J Dermatol. 1955; 67: 53-59
        • Ricci G.
        • Patrizi A.
        • Giannetti A.
        • Dondi A.
        • Bendandi B.
        • Masi M.
        Does improvement management of atopic dermatitis influence the appearance of respiratory allergic diseases? A follow-up study.
        Clin Mol Allergy. 2010; 8: 8
        • Garmhausen D.
        • Hagemann T.
        • Bieber T.
        • et al.
        Characterization of different courses of atopic dermatitis in adolescent and adult patients.
        Allergy. 2013; 68: 498-506
        • Hartwig I.R.
        • Sly P.D.
        • Schmidt L.A.
        • et al.
        Prenatal adverse life events increase the risk for atopic diseases in children, which is enhanced in the absence of a maternal atopic predisposition.
        J Allergy Clin Immunol. 2014; 134: 160-169
        • Aberg N.
        • Engstrom I.
        Natural history of allergic diseases in children.
        Acta Paediatr Scand. 1990; 79: 206-211
        • Ziyab A.H.
        • Raza A.
        • Karmaus W.
        • et al.
        Trends in eczema in the first 18 years of life: results from the Isle of Wight 1989 birth cohort study.
        Clin Exp Allergy. 2010; 40: 1776-1784
        • Peters A.S.
        • Kellberger J.
        • Vogelberg C.
        • et al.
        Prediction of the incidence, recurrence, and persistence of atopic dermatitis in adolescence: a prospective cohort study.
        J Allergy Clin Immunol. 2010; 126 (e1–e3): 590-595
        • Musgrove K.
        • Morgan J.K.
        Infantile eczema: a long-term follow-up study.
        Br J Dermatol. 1976; 95: 365-372
        • Rystedt I.
        Long term follow-up in atopic dermatitis.
        Acta Derm Venereol Suppl (Stockh). 1985; 114: 117-120
        • Mortz C.G.
        • Andersen K.E.
        • Dellgren C.
        • Barington T.
        • Bindslev-Jensen C.
        Atopic dermatitis from adolescence to adulthood in the TOACS cohort: prevalence, persistence and comorbidities.
        Allergy. 2015; 70: 836-845

      Linked Article

      • Conclusions about atopic dermatitis persistence might be premature
        Journal of the American Academy of DermatologyVol. 76Issue 5
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          To the Editor: We read the review by Kim et al1 and applaud the authors for addressing this important challenging topic. It is well known that atopic dermatitis (AD) is a condition whereby patients often have episodic flares and that some patients might have prolonged periods without symptoms followed by recurrences.2 The relapsing nature of AD complicates the measurement of disease activity over time and the average frequency and duration of asymptomatic periods is variable and poorly defined. For these reasons, the definition of persistence is not straightforward, and a meta-analysis on this topic requires careful consideration of methodologic issues and clear explanations of terminology.
        • Full-Text
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      • Heterogeneity of data included in meta-analysis on persistence of atopic dermatitis changes interpretation
        Journal of the American Academy of DermatologyVol. 76Issue 5
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          To the Editor: We enjoyed reading Persistence of atopic dermatitis (AD): A systematic review and meta-analysis but have concerns.1,2 The goal of this publication was to determine if childhood AD persists through life.2 The study combined data from about 44 studies. The term pooled is used in this publication, which usually refers to the pooling of individual level data; however, the analysis appears to pool study data.2,3 We feel strongly that the results of this study should be interpreted with caution.
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